Pseudomonas aeruginosa is a species of typical resident microbiota which exists in the natural environment, and is well known as a pathogen causing opportunistic infections in immune-compromised humans. In addition, Pseudomonas aeruginosa is one of the species that are most problematic from the high isolation rate and mortality rate in healthcare-associated infections. It has been reported that the isolation rate for Pseudomonas aeruginosa is the sixth highest out of all healthcare-associated pathogenic infections and the second highest for patients having pneumonia derived from tracheal intubation, and the mortality rate due to Pseudomonas aeruginosa is 27.6-47.9% in bloodstream infections and 42.1-87% in tracheal intubation (Non-Patent Literatures 1 to 3). Further, since Pseudomonas aeruginosa originally had a high resistance to disinfectants and antibiotics and there are many strains that have acquired drug resistance, it is often difficult to treat the pseudomonal infections. Antimicrobial agents for Pseudomonas aeruginosa include carbapenems, cephems, penicillins, quinolones, and the like, and the resistance rate against these antimicrobial agents is a high rate such as 25.3%, 11.2%, 17.5%, and 30.7%, respectively (Non-Patent Literature 1). There is therefore a demand for a new anti-pseudomonas aeruginosa drug which is also effective against multidrug-resistant Pseudomonas aeruginosa, especially since there are almost no antimicrobial agents effective against multidrug-resistant bacteria showing a resistance to the above antimicrobial agents.
Pseudomonas aeruginosa is a gram-negative bacterium having a lipopolysaccharide (LPS) on the surface layer, and a sugar chain structure called O antigen outside of this LPS. The O-antigen has antigenicity and because of its diversity, it has been used as a classification method for bacterial strains (Non-Patent Literatures 4 and 5). In general 20 species of the LPS O antigen serotype of Pseudomonas aeruginosa are known, and in recent years, it has been reported that the strains having O11 antigen (O11 strains) occupy a high ratio in the multidrug-resistant Pseudomonas aeruginosa. In Japan there are reports that the isolation rates of O11 stains in the multidrug-resistant Pseudomonas aeruginosa were 99% or about 60%, and in Europe such as France, Belgium, and Czech Republic, there are also reports that a number of multidrug-resistant Pseudomonas aeruginosa strains were O11 strains (Non-Patent Literatures 6 to 11).
Antibodies are known to provide long-term protection against infection in vivo. Many antibodies against the LPS O antigens of Pseudomonas aeruginosa have been reported to exhibit a therapeutic efficacy by their opsonophagocytic killing activities on infections in an animal infectionmodel (Non-Patent Literatures 12 to 14). From this, such antibodies against the LPS O11 antigens of Pseudomonas aeruginosa are expected to be a new drug against multidrug-resistant Pseudomonas aeruginosa, and there are already some reports on anti-LPS O11 antibodies (Patent Literatures 1 and 2).
The present invention relates to a therapeutic and diagnostic antibody that targets the Pseudomonas aeruginosa O11 strain. The therapeutic and diagnostic antibody is desired to have a high activity, and its opsonophagocytic killing activity is important. Further, antibodies are known to have high antigen specificity, and those having a high coverage ratio capable of broadly covering the O11 strains are desired as a therapeutic and diagnostic antibodies. Since the present antibodies are antibodies to the LPS O11 antigens and show a stronger opsonophagocytic killing activity and a higher coverage ratio compared to conventional antibodies, they are more useful.